HER-2 exon 20 mutation

PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications.

The management of human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) remains a significant clinical challenge, with limited effective and accessible treatment options beyond antibody-drug conjugates such as trastuzumab deruxtecan (T-DXd)...Following chemotherapy and sintilimab failure in August 2025 due to progressive disease, furmonertinib rechallenge at 160 mg/day again induced a response within 5 days, with no grade ≥3 adverse events...The structural homology between HER2 p.Y772_A775dup and EGFR exon 20 "near-loop" insertions may facilitate TKI binding. Furmonertinib emerges as a potential, cost-effective oral therapeutic alternative for this patient population, especially when standard therapies are not feasible, warranting further prospective investigation.

P1, N=200, Recruiting, Nuvalent Inc. | N=150 --> 200 | Trial completion date: Mar 2026 --> Feb 2027 | Trial primary completion date: Mar 2026 --> Jan 2027

P2, N=61, Not yet recruiting, Guangdong Association of Clinical Trials

P2, N=27, Enrolling by invitation, Yonsei University | Not yet recruiting --> Enrolling by invitation | Trial completion date: Apr 2026 --> Dec 2026 | Trial primary completion date: Jan 2026 --> Dec 2026

This case shows that perioperative treatment with T-DXd could induce tumor regression and sustain remission, while MRD monitoring enables early detection of molecular progression. These findings emphasize the potential of combining T-DXd and MRD monitoring to tailor treatment to improve outcomes in HER2-mutant NSCLC.

This study firstly supplements real-world evidence on T-DXd treatment in Chinese patients with previously treated HER2-mutant advanced NSCLC. The results preliminarily showed the favorable antitumor activity and acceptable safety profile of T-DXd in clinical practice.

She achieved a partial response within one month and has maintained disease control for over 31 months, with only mild intermittent diarrhea. This case provides real-world evidence supporting the potential of pyrotinib as an effective first-line treatment for HER2-mutant NSCLC, particularly in patients with the Y772_A775dup variant and concurrent EGFR alterations, and highlights the need for further clinical investigation in this setting.

Single-agent neratinib has limited activity in ERBB2-mutated lung cancers. Combinations with temsirolimus or trastuzumab did not markedly improve overall outcomes, producing durable responses in a limited subset of patients.

She received eight additional cycles (nine in total), resulting in tumor regression without ILD recurrence. Given that T-DXd is currently the only approved HER2-targeted therapy for NSCLC in our country, this case underscores the importance of early detection and appropriate management of ILD to maximize the therapeutic benefits.

We furthermore demonstrate the activity of sevabertinib in a cancer cell line dependent on a fusion of NRG1, a ligand for the HER2 family member and heterodimerization partner, HER3. Finally, we report patient responses to sevabertinib from a Phase 1/2 clinical trial, indicating potential benefit for patients with HER2-mutant lung cancer.

In recent years, novel antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), have demonstrated groundbreaking efficacy in HER-2-mutant advanced NSCLC patients...The consensus also includes detailed recommendations for screening and managing adverse effects associated with ADCs, such as interstitial lung disease (ILD), emphasizing the crucial role of safety management in ensuring treatment efficacy. The publication of this consensus aims to drive the standardization of molecular diagnosis and treatment pathways for HER-2 variant NSCLC, improve clinical outcomes and quality of life for patients, and facilitate the implementation of personalized precision treatment strategies.